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Menon V. (2015) Salience Network. In: Arthur W. Toga, editor. Brain Mapping:
An Encyclopedic Reference, vol. 2, pp. 597-611. Academic Press: Elsevier.
 Author's personal copy
Salience Network
V Menon, Stanford University School of Medicine, Stanford, CA, USA
2015 Elsevier Inc. All rights reserved.
Introduction and Overview
The human brain consists of multiple, distinct, and interacting
networks; investigation of these networks has provided a
systematic framework for understanding fundamental aspects
of human brain organization and function (Bressler & Menon,
2010). In this context, identification and characterization of the
salience network (SN) have contributed greatly to our under-
standing of core brain systems involved in identification of
biologically and cognitively relevant events to guide flexible
behavior (Menon & Uddin, 2010; Seeley et al., 2007).
The SN is an intrinsically connected large-scale network
anchored in the anterior insula (AI) and dorsal anterior cingulate
cortex (dACC; Figure 1). The SN also includes three key subcor-
tical structures: the amygdala, the ventral striatum, and the
substantia nigra/ventral tegmental area. Crucially, a network
perspective helps integrate the explosive and wide range of
brain imaging studies that have implicated these regions, most
notably the AI and dACC, in multiple, often disparate, cognitive
and affective processes. The SN, together with its interconnected
brain networks, contributes to a variety of complex brain func-
tions, including communication, social behavior, and self-
awareness through the integration of sensory, emotional, and
cognitive information (Craig, 2009; Gogolla, Takesian, Feng,
Fagiolini, & Hensch, 2014; Menon & Uddin, 2010).
This article summarizes recent progress in our understand-
ing of the SN; its functional and structural organization; its role
in cognition, emotion, and development; and its disruption in
psychopathology. I begin with a brief outline of saliency and
general saliency detection mechanisms in the brain. I then
focus on identification of the SN, highlighting its key nodes
and their functional and structural connectivity patterns. I
describe the core functions of this network in attention and
cognitive control, focusing on the AI as a dynamic hub for
detection and selection of salient stimuli and for mediating
interactions with other neurocognitive systems. I will then
highlight its crucial role in switching between systems involved
in processing exogenous and self-relevant information and
briefly discuss key features of SN development from infancy
to adulthood, concluding with an examination of how charac-
terization of SN dysfunction is leading to a more thorough
understanding of psychopathology.
Saliency Detection and the Salience Network
Two General Mechanisms of Saliency Detection
The nervous system dynamically selects specific stimuli for
additional processing from a constant stream of incoming sen-
sory inputs. Saliency detection mechanisms in the brain are at
the core of this process and can be conceptualized into two
general mechanisms. The first is a fast, automatic, bottom-up
primitive mechanism for filtering stimuli based on their per-
ceptual features (Peters, Iyer, Itti, & Koch, 2005). Filtering and
amplification of stimuli can, in principle, occur at multiple
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Brain Mapping: An Encyclopedic Reference, (2015), vol. 2, pp. 597-611
levels in the hierarchy of ascending neural pathways that
bring stimuli from the external world to the sensory cortex. At
each level, salience filters enhance responses to stimuli that are
infrequent in space or time or are of learned or instinctive
biological importance (Knudsen, 2007). For example, neurons
in the superior colliculi can amplify responses to specific visual
stimuli based on stimulus-driven representations in local
salience maps (Fecteau, Bell, & Munoz, 2004). The neural
mechanisms for this level of saliency detection include adapta-
tion to repeated stimuli and center-surround properties of local
circuits. The second is a higher-order system for competitive,
context-specific, stimulus selection and for focusing the
spotlight of attention and enhancing access to resources
needed for goal-directed behavior. The large-scale network
described here is a core brain system that implements this latter
process. The SN described here is a paralimbiclimbic network
that is distinct from the dorsal spatial attention network, a
system anchored in the intraparietal sulcus and frontal eye
fields that helps maintain a stable saliency or priority map of
the visual environment (Egner et al., 2008; Fecteau & Munoz,
2006; Ptak, 2012; Szczepanski, Pinsk, Douglas, Kastner, &
Saalmann, 2013). Within the context of the SN, events that are
likely to be perceived as salient include deviants embedded in
a constant stream, surprising stimuli, and stimuli that are plea-
surable and rewarding, self-relevant, or emotionally engaging.
Conceptualizing Saliency in Psychopathology
A consideration of saliency in the context of psychopathology
serves to illustrate its subjective and self-referential nature.
Crucially, it helps highlight the notion that an event that is
salient for one group of individuals may not be salient for
another. For example, in individuals with autism, the relative
salience of social stimuli, such as face, eyes, and gaze, may be
diminished, leading to poor social skills (Volkmar, 2005). On
the other hand, for a hypersocial child with Williams syn-
drome, exactly the opposite may be true (Jabbi et al., 2012).
To take a few more examples, specific drug paraphernalia may
be uniquely salient to individuals with a cocaine addiction but
not to individuals with anxiety or pain. In schizophrenia, mis-
attribution of salience to external and internal stimuli is a core
feature of the disorder and may explain the genesis of psychotic
symptoms such as delusions and hallucinations (Palaniyappan
& Liddle, 2012). Thus, saliency has several subjective and
psychopathology-specific attributes, and within the context of
the SN, aberrant saliency detection has important repercus-
sions for how exogenous and internal cues are processed and
attended to (Menon, 2011), a topic that we explore further in
Section Typical and Atypical Development of the SN.
Salience Network: Identification and Anatomical Basis
The SN is most readily identified using intrinsic functional
connectivity analysis of fMRI data acquired when a subject is
597
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598 INTRODUCTION TO SYSTEMS | Salience Network

10

z = 32 x = 6 y = 14 z = 2 z = 50 x = 48 y = 62 x = 30
(a) (b)

z = 40 x = 40 y = 38 x = 38
(c) z = 38 x = 42 y = 10 z = 38
(d)
(A) (B)

Figure 1 Salience network identification using independent component analysis. (A) (a) The salience network (SN) is readily identified as an
intrinsically connected large-scale network that is distinct from (b) the dorsal attention network anchored in the frontal eye field and intraparietal sulcus
and (c, d) the left and right lateral frontoparietal central executive networks. (B) Cortical and subcortical nodes of the salience network (shown
in red). The salience network has distinct patterns of intrinsic cortical and subcortical connectivity from the lateral frontoparietal central executive
network in the anterior thalamus (antTHAL), dorsal caudate nucleus (dCN), dorsomedial thalamus (dmTHAL), hypothalamus (HT), periaqueductal gray
(PAG), putamen (Put), sublenticular extended amygdala (SLEA), substantia nigra/ventral tegmental area (SN/VTA), and temporal pole (TP).
Adapted from Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., et al. (2007). Dissociable intrinsic connectivity networks
for salience processing and executive control. The Journal of Neuroscience, 27, 23492356; Shirer, W. R., Ryali, S., Rykhlevskaia, E., Menon, V., &
Greicius, M. D. (2011). Decoding subject-driven cognitive states with whole-brain connectivity patterns. Cerebral Cortex, 22, 158165.

at rest (i.e., not performing any specific task). This analysis
overcomes a limitation of task-based brain imaging data, in
which the SN has been difficult to disentangle from other
neurocognitive networks because of coactivations of the insula,
dACC, dorsolateral and ventrolateral prefrontal cortices, fron-
tal eye fields, and intraparietal sulcus across a wide range of
cognitive tasks (Chang, Yarkoni, Khaw, & Sanfey, 2013; Dosen-
bach et al., 2006). Intrinsic functional connectivity analysis has
provided evidence for a distinct paralimbiclimbic network of
strongly coupled brain areas (Dosenbach et al., 2007; Seeley
et al., 2007; Figure 1).
The SN is most readily identified using independent com-
ponent analysis of resting-state fMRI data (Seeley et al., 2007;
Sridharan, Levitin, & Menon, 2008). This network includes
prominent nodes in the AI and dACC, distinct from the central
executive network anchored in the lateral frontoparietal cortex
and the dorsal spatial attention network anchored in the
frontal eye field and intraparietal sulcus (Seeley et al., 2007;
Shirer, Ryali, Rykhlevskaia, Menon, & Greicius, 2012). The SN
also includes distinct limbic areas including the amygdala,
ventral striatum, dorsomedial thalamus, hypothalamus, and
substantia nigra/ventral tegmental area (Seeley et al., 2007;
Figure 1). Seed-based intrinsic functional connectivity analysis
of its major nodes also reliably reproduces the core cortical
nodes of the network, and subcortical nodes in the ventral
striatum and ventral tegmental area can also be detected albeit
at a weaker level (Figure 2).
Intrinsic connectivity and task-related meta-analytic inves-
tigations have consistently divided the insula into three sub-
divisions, encompassing its dorsalanterior, ventralanterior,
and posterior aspects (Chang et al., 2013). The AI node of the
SN corresponds most closely with the dorsalanterior insular
(Chang et al., 2013; Deen, Pitskel, & Pelphrey, 2011; Figure 3),
and results from multiple methodologies have shown that the
dorsalanterior AI has particularly robust connectivity with the
dACC (Brodmann area 24) node of the SN (Figure 3).
Further evidence for segregation of the SN from other net-
works comes from diffusion tensor imaging studies, which
have identified white matter tracts connecting the AI to dACC
along the uncinate fasciculus and extending more dorsally to
the medial aspects of the frontal lobe (Uddin, Supekar, Ryali, &
Menon, 2011; Van Den Heuvel, Mandl, Kahn, & Hulshoff Pol,
2009). These tracts are distinct from the fronto-occipital and
superior longitudinal fasciculi, which connect the dorsolateral
frontoparietal central executive network (Figure 4). This limbic
pathway is critical for processing novel information and
enabling interaction between cognition, emotion, and action
(Mori, Oishi, & Faria, 2009; Schmahmann et al., 2007). The
precise white matter pathways linking cortical and subcortical
nodes of the SN in the human brain have yet to be delineated,
but there is considerable evidence from nonhuman primates
for such tracts, including other segments of the uncinate fas-
ciculus, which link the AI with the amygdala and anterior
temporal lobe (Mesulam & Mufson, 1982; Nieuwenhuys,
2012; Schmahmann & Pandya, 2009).
It is further noteworthy that the structural architecture of
the AI and dACC shares unique features at the cellular level. In
the human brain, the AI and dACC contain a specialized class
of neurons, the von Economo neurons (VENs), with distinctive
anatomical and functional properties (Allman et al., 2010;
Nimchinsky et al., 1999; Figure 5). The VENs have wider
axons, which can facilitate rapid relay of signals from the AI
and dACC to other cortical regions (Allman, Watson, Tetreault,
& Hakeem, 2005), endowing the SN with distinct mechanisms
for signaling within and across the SN.
The Salience Network Modes Are Commonly
Coactivated Across a Wide Range of Cognitive
and Affective Tasks
The AI and dACC are among the most frequently activated
regions in all of functional neuroimaging research
(Buchsbaum, Greer, Chang, & Berman, 2005; Dosenbach
et al., 2006; Nelson et al., 2010; Smith et al., 2009; Supekar &
Menon, 2012; Wager et al., 2005; Yarkoni, Poldrack, Nichols,

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INTRODUCTION TO SYSTEMS | Salience Network 599

dACC

VStr

y = +18 AI y = +6 y = 20
VTA

z = +4 z = +4 z = 14
(a) (b) (c)

Figure 2 Salience network identified using right anterior insula (AI) connectivity. (a) The AI shows high levels of correlation (r > 0.3) with the right
anterior insula (AI) seed (MNI coordinates: 36, 18, 4) (y 18 and z 4). (b) At lower thresholds (r < 0.2), AI connectivity is also evident in the
ventral striatum (VStr; y 6 and z 4) and (c) ventral tegmental area (VTA; z 20 and z  14). Image generated from a sample of 1000 subjects
using Neurosynth.org, based on Yeo et al. (2011).

Van Essen, & Wager, 2011). To illustrate this, I used the
Neurosynth database to conduct a search using the right AI
node of the SN (MNI coordinate: x 36, y 18, z 4). The
search revealed significant AI activation across a wide range of
tasks, with over 400 descriptive features ranging from pain to
go-no-go, number, letter, counting, and anticipation (Figure 6).
Crucially, the AI and dACC show strong functional covariance
across a wide range of tasks (Cauda et al., 2011; Chang et al.,
2013; Deen et al., 2011). Consistent with these findings, meta-
analytic coactivation analysis of the AI also revealed prominent
overlap in cortical and subcortical nodes of the SN (Figure 7).
Integrated Salience Network Function in Cognition,
Action, and Emotion
SN responses show close correspondence between intrinsic
connectivity and task-related coactivation patterns (Figures 1,
2, and 7). This correspondence allows intrinsic and task-related
fMRI activations associated with the SN to be identified and
studied in a common framework (Bonnelle et al., 2012; Ham,
Leff, De Boissezon, Joffe, & Sharp, 2013; Sridharan et al., 2008;
Supekar & Menon, 2012). Despite this similarity and their
largely common pattern of activation, until recently, the AI
and dACC were thought to be part of different functional
systems. The AI was typically associated with social and affec-
tive tasks involving pain, empathy, disgust, and introspective
processes (Craig, 2009; Singer, Critchley, & Preuschoff, 2009),
whereas the dACC was most closely associated with response
selection, conflict resolution, and cognitive control (Botvinick,
Cohen, & Carter, 2004). Identification of the AI and dACC as
core nodes of the SN in the intrinsic state and their concurrent
activation across a wide range of tasks has led to a more
integrated view of the function of these regions. This section
describes an integrative model of SN function predicated on
the conjoint activations, but differential inputs, outputs,
and putative roles, of its major nodes in cognition, action,
and emotion (Figure 8).
Detection and Integration of Salient Sensory Cues: Differential
Role of the AI
The two main cortical nodes of the SN serve distinct functions
by virtue of their differential inputs and outputs. The AI
receives convergent input from multiple sensory modalities
including auditory and visual systems (Augustine, 1996;
Bamiou, Musiek, & Luxon, 2003; Butti & Hof, 2010; Mesulam
& Mufson, 1982; Nieuwenhuys, 2012), and there is converging
evidence from human neuroimaging studies for its involve-
ment in simultaneous attention to multisensory stimuli
(Bushara, Grafman, & Hallett, 2001; Bushara et al., 2003).
Other major sources of input include the amygdala, ventral
striatum, and the ventral tegmental nuclei, constituting the key
subcortical nodes of the SN, which provide access to the emo-
tional and reward saliency of stimuli. Crucially, in addition to
its response to external stimuli, the insula is also sensitive to
internal signals associated with autonomic processes such as
heartbeat, skin conductance, and respiration (Critchley, Eccles,
& Garfinkel, 2013; Singer et al., 2009). These autonomic pro-
cesses have been linked to interceptive awareness of salient
events and likely involve interactions of the SN with the pos-
terior insula (Figure 9).
A major function of the AI node of the SN is the detection of
behaviorally relevant stimuli. Influential models of attention
have long postulated a key role for the right fronto-opercular
cortex in orienting attention (Corbetta, Patel, & Shulman,
2008), but recent studies have more directly associated the AI
subdivision with saliency detection (Crottaz-Herbette &
Menon, 2006; Eckert et al., 2009; Seeley et al., 2007; Sridharan
et al., 2008; Sterzer & Kleinschmidt, 2010). Detection of

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600 INTRODUCTION TO SYSTEMS | Salience Network

Figure 3 Anatomical localization and connectivity of the anterior insula node of the salience network. (a) Three major functional subdivisions of the insular
cortex identified using intrinsic connectivity analysis: dorsalanterior insula (blue), ventralanterior insula (red), and posterior insula (green).
The dorsalanterior insula corresponds most closely to the AI node of the SN. (b) (A) Cytoarchitectonic gradient from the agranular cortex in the anterior
inferior insula via the dysgranular cortex to the granular cortex in the posterior insula. (B) Approximate boundaries and putative functions of the three
insula subdivisions. Adapted from Deen, B., Pitskel, N. B., & Pelphrey, K. A. (2011). Three systems of insular functional connectivity identified with cluster
analysis. Cerebral Cortex, 21, 14981506; Chang, L. J., Yarkoni, T., Khaw, M. W., & Sanfey, A. G. (2012). Decoding the role of the insula in human
cognition: Functional parcellation and large-scale reverse inference. Cerebral Cortex, 23, 739749; Klein, T. A., Ullsperger, M., & Danielmeier, C. (2013).
Assessing error awareness without relying on introspective judgment? Frontiers in Neuroscience, 7, 113. (c) (A) Intrinsic functional connectivity of the three
insula subdivisions illustrating largely segregated systems associated with the AI node of the salience network (shown in blue). Networks associated
with the three insula subdivisions are largely segregated in the resting state. (B) Similar profiles are observed in meta-analytic coactivation analysis
of task-based fMRI data. Although networks associated with the three insula subdivisions are largely segregated during active tasks, they show prominent
overlap in the posterior insula, basal ganglia, and thalamus. Adapted from Chang, L. J., Yarkoni, T., Khaw, M. W., & Sanfey, A. G. (2012). Decoding the
role of the insula in human cognition: functional parcellation and large-scale reverse inference. Cerebral Cortex, 23, 739749.

behaviorally salient relevant stimuli is an essential component
of almost all cognitive tasks. Consistent with this view, meta-
analysis of a wide range of attention tasks, including the canon-
ical oddball task, which involves detection of deviant stimuli
embedded in a stream of standard stimuli (Crottaz-Herbette &
Menon, 2006; Debener, Kranczioch, Herrmann, & Engel,
2002; Kiehl & Liddle, 2003; Yago, Duarte, Wong, Barcelo, &
Knight, 2004), and cognitive control tasks, such as the stop
signal and go-no-go tasks, have revealed that the AI and dACC
are consistently coactivated across many different cognitive
paradigms (Swick, Ashley, & Turken, 2011).
Response Selection and Monitoring: Differential Role
of the dACC
In contrast to the AI, the dACC node of the SN is more directly
involved in response selection and conflict monitoring (Ide,
Shenoy, Yu, & Li, 2013). A wide range of functional imaging
studies and theoretical models have suggested that the ACC
plays a prominent role in action selection (Rushworth, 2008).
An examination of the pattern of inputoutput connectivity of
the AI and the ACC provides further insights into the differen-
tial functions of the AI and dACC. While the AI receives mul-
timodal sensory input, the dACC and associated dorsomedial
prefrontal cortex receive very little such inputs (Averbeck &
Seo, 2008; Vogt & Pandya, 1987). Conversely, while the ACC
and associated dorsomedial prefrontal cortex send strong
motor output, there is relatively little direct motor output
from the AI. Furthermore, the ACC and dorsomedial prefrontal
cortex have direct connections to the spinal cord and sub-
cortical oculomotor areas (Fries, 1984), giving them direct
control over action. With these differential anatomical path-
ways and von Economo neurons that facilitate rapid signaling
between the AI and the ACC, the SN is well positioned to

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INTRODUCTION TO SYSTEMS | Salience Network 601

Adult 1 Adult 2 Adult 3 Adult 4

(a)
Number of
SN Group DTI
subjects
>15
12
8
4
1
(b)

Figure 4 Structural connectivity between salience network nodes. (a) White matter pathways between the extended frontoinsular cortex, including the
AI node of the SN, and ACC, including the dACC node of the SN. DTI tractography reliably identified ventral white matter tracts overlapping with the
uncinate fasciculus. Fibers (blue) connecting the frontoinsular cortex (red) and ACC (green) in representative adults. The first row shows sagittal slices
viewed from the right, and the second row shows coronal slices viewed anteriorly. These tracts were detected in 11 of 15 adults (73%). Adapted
from Uddin, L. Q., Supekar, K. S., Ryali, S., & Menon, V. (2011). Dynamic reconfiguration of structural and functional connectivity across core
neurocognitive brain networks with development. The Journal of Neuroscience, 31, 1857818589. (b) Dorsal tracts linking the frontoinsular cortex and
ACC. Adapted from Van Den Heuvel, M. P., Mandl, R. C., Kahn, R. S., & Hulshoff Pol, H. E. (2009). Functionally linked resting-state networks reflect
the underlying structural connectivity architecture of the human brain. Human Brain Mapping, 30, 31273141.

Figure 5 Specialized neurons in the AI and dACC nodes of the salience network. (a) Regions of the brain containing von Economo neurons (VENs). (A)
Lateral view with the frontoinsular cortex (FI) shown in red. (B) Medial view with the anterior cingulate cortex (ACC) shown in red. Adapted from Allman,
J. M., Watson, K. K., Tetreault, N. A., & Hakeem, A. Y. (2005). Intuition and autism: A possible role for Von Economo neurons. Trends in Cognitive
Sciences, 9, 367373. (b) MRI cross sections showing the location of the VEN-containing AI and dACC areas in the right hemisphere of a young adult
human female. (AC) MRI sections are frontal, horizontal, and parasagittal sections that intersect in the AI. (D, E) Three-dimensional reconstructions
of the left hemisphere. Adapted from Allman, J. M., Tetreault, N. A., Hakeem, A. Y., Manaye, K. F., Semendeferi, K., Erwin, J. M., et al. (2010). The von
Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Structure and Function, 214, 495517.
Brain Mapping: An Encyclopedic Reference, (2015), vol. 2, pp. 597-611
 Author's personal copy

Letter Heat
Go-nogo
Load
Go
No-go
Decision-making

Noxious

Counting

Number 6
5
4 Anticipation
3
Pain 2
1
Abilities

Painful

Working

Phonological

Verbal

Readers

Verb

Rehearsal
Unpleasantness
Sensation
Temperature
Short-term Somatosensory
Figure 6 Polar plot illustrating the wide range of cognitive and affective tasks that engage the salience network. Data based on meta-analysis of the
same right AI seed (MNI coordinates: 36, 18, 4) as in Figure 2. Z-scores correspond to likelihood of specific task-based terms in the Neurosynth
database.

dACC

VStr

y = +18 y = +6 y = 20

VTA

(a) z = +4 (b) z = +4 (c) z = 14

Figure 7 Task-related coactivation of salience network nodes. (a) Cortical nodes in the AI and dACC show high levels of task-related
coactivation (y 18 and x 4). At lower thresholds, coactivation is also evident in (b) the ventral striatum (VStr; y 6 and z 4) and (c) ventral
tegmental area (VTA; z 20 and z 4). Slice locations are the same as in Figure 2. Image generated using Neurosynth.org.

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INTRODUCTION TO SYSTEMS | Salience Network 603

Salience Network

Sensory Afferents Motor Efferents

AI dACC
Pre-SMA, MCC

Visceral Afferents Affective-Motivational Visceral Efferents

pl Amgydala, VStr/VTA HT, PAG

Figure 8 Summary of salience network organization in relation to its major afferents and efferents. The AI receives convergent multisensory inputs,
affective and motivational signals, and visceral afferents, reflecting biological saliency and cognitive demands. In contrast, the dACC plays a more
dominant role in response selection, guiding overt behavior and modulating autonomic reactivity. AI, anterior insula; dACC, dorsal anterior
cingulate cortex; HT, hypothalamus; PAG, periaqueductal gray; pI, posterior insula; VStr, ventral striatum; VTA, ventral tegmental area. Adapted from
Menon, V., & Uddin, L. Q. (2010). Saliency, switching, attention and control: A network model of insula function. Brain Structure and Function,
214, 655667; Zhou, J., & Seeley, W. W. (2014). Network dysfunction in Alzheimers disease and frontotemporal dementia: Implications for psychiatry.
Biological Psychiatry, 75, 565573.

L R plns
MCC

ALE-value Angular Prec/

0.025 z = 44 z = 22 gyrus z = 12 vPCC
0
pgACC
alns alns/ sgACC/
FIC vmPFC
VTA/
Hyp
mdThal

Pulvinar SC/
PAG Amygdala
z=6 z = 6 z = 20
Figure 9 Cortical and subcortical regions associated with autonomic processing overlap with the salience network. Meta-analyses of studies showing
general brain regions involved in autonomic processing. Prec, precuneus; vPCC, ventral posterior cingulate cortex; mdThal, mediodorsal
thalamus; pgACC, pregenual ACC; VTA, ventral tegmental area; Hyp, hypothalamus; SC, superior colliculus; PAG, periaqueductal gray; FIC, frontoinsular
cortex; L, left; R, right. Adapted from Beissner, F., Meissner, K., Bar, K. J., & Napadow, V. (2013). The autonomic brain: An activation likelihood
estimation meta-analysis for central processing of autonomic function. The Journal of Neuroscience, 33, 1050310511.

influence not only attention but also motor responses to
salient sensory stimuli.
Integration of Salient Affective Cues: Inputs from Subcortical
Nuclei
The major subcortical nodes of the SN the amygdala, ventral
striatum, and ventral tegmental area provide preferential
context-specific access to affective and reward cues. These
cues include biasing signals from the amygdala associated
with negatively valenced stimuli and the nucleus accumbens
and ventral tegmental area signals associated with reward
(Lindquist, Wager, Kober, Bliss-Moreau, & Barrett, 2012). A
more general view of this organization is that emotional and
motivational signals can be embedded into the SN through
multiple channels (Pessoa, 2014), allowing preferential access
to affective cues within the cognitionaction mechanisms sub-
served by the AI and dACC, the two major cortical nodes of the

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604 INTRODUCTION TO SYSTEMS | Salience Network

SN. Comparatively, little is known, however, about the integra-
tive role of the subcortical nuclei in the context of SN function,
and this remains an important area for future research, espe-
cially with respect to social and affective processes.
Dynamic Interaction of the SN with Other Brain
Networks: Evidence for Switching Networks
The SN not only plays an important role in saliency detection
and reactivity but also facilitates access to attention and working
memory resources once a salient event has been detected.
Emerging evidence suggests that the SN plays a crucial role in
switching between large-scale brain networks involved in exter-
nally oriented attention and internally oriented mental processes
(Sridharan et al., 2008). During the performance of many
cognitively demanding tasks, the SN, together with the lateral
frontoparietal central executive network, typically shows
increase in activation, whereas the default-mode network
shows consistent decrease in activation below the resting base-
line (Greicius, Krasnow, Reiss, & Menon, 2003; Greicius &
Menon, 2004; Raichle et al., 2001). Importantly, brain responses
within these regions increase and decrease proportionately and
often antagonistically, in relation to specific cognitive demands
and subjective task difficulty. Once a salient event is detected, the
AI facilitates sustained processing by initiating appropriate tran-
sient control signals that engage cognitive and task control sys-
tems while suppressing the default-mode network (Sridharan
et al., 2008). The right AI node of the SN, in particular, has
been shown to be a causal hub for signaling the dorsal fronto-
parietal central executive network (Figure 10), a system impor-
tant for maintaining and manipulating information in working
memory (DEsposito, 2007; Fuster, 2000; Goldmanrakic, 1995;
Miller & Cohen, 2001; Smith & Jonides, 1998).
The most dramatic evidence for the role of the SN in medi-
ating the dynamic interaction between networks comes from
studies of patients with traumatic brain injury. Bonnelle and
colleagues found that abnormal default-mode network func-
tion was specifically predicted by the amount of white matter
damage in the SN tract connecting the right AI to the dACC and
presupplementary motor area (Bonnelle et al., 2012). These
results provide evidences that structural integrity of the SN is
necessary for the efficient regulation of activity in the default-
mode network and that a failure of this regulation leads to
inefficient cognitive control and weaker performance on cog-
nitive control tasks. Critically, these switching mechanisms
help focus attention on task-relevant stimuli and goals, and
as a result, they take on added significance or saliency (Menon
& Uddin, 2010; Figure 11).
Typical and Atypical Development of the SN
A thorough understanding of the SN requires critical consider-
ation of the developmental pathways by which plasticity and
learning lead to the construction of this dedicated large-scale
brain system. Although the study of brain network develop-
ment is still in its infancy, new studies are beginning to shed
light on the typical and atypical developmental trajectories of
this network. The SN can be readily identified by age 2, but it
undergoes protracted changes in connection strength through-
out childhood (Gao et al., 2013). Between the ages 7 and 20,
the SN undergoes further developmental changes that span
both within- and across-network links (Uddin et al., 2011).
Analysis of these links provides unique insights into the

Visual oddball attention task

3

2.5 rAI

1.5
ACC PCC
(Out-in) degree

0.5

0.5 VMPFC rPPC

1.5
rDLPFC
2
rFIC ACC rDLPFC rPPC VMPFC PCC
Figure 10 Net causal outflow of major nodes of the salience, central executive, and default-mode networks. (a) Dynamical systems analysis
reveals that the right anterior insula (AI) has a significantly higher net causal outflow than any of the nodes of the central executive or default-mode
networks. (b) Granger causal analysis of connectivity showed significant causal outflow from the right AI to major nodes of the two other
networks. These results, together with latency analyses, suggest that the rAI functions as a causal outflow hub for salient events. Adapted from
Sridharan, D., Levitin, D. J., & Menon, V. (2008). A critical role for the right fronto-insular cortex in switching between central-executive and
default-mode networks. Proceedings of the National Academy of Sciences of the United States of America, 105, 1256912574.

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 Author's personal copy
INTRODUCTION TO SYSTEMS | Salience Network 605

Figure 11 Dynamic salience network-mediated switching of large-scale brain networks. The salience network (SN) plays a crucial role in
dynamic switching between the central executive and default-mode networks. The SN recruits the central executive and task control regions to maintain
cognitive set and manipulate information in working memory while suppressing the default-mode network to keep attention focused on task-
relevant goals. Adapted from Bressler, S. L., & Menon, V. (2010). Large-scale brain networks in cognition: Emerging methods and principles. Trends in
Cognitive Sciences, 14, 277290.

maturation of core neurocognitive systems. Compared with
adults, children show significantly weaker functional connectiv-
ity between the AI and dACC (within the SN) and the AI and
dorsolateral prefrontal cortex and posterior cingulate cortex
(between the SN and other networks). Notably, the AI is the
only node that shows significant age-related differences in func-
tional connectivity between the SN and other networks, suggest-
ing that this region is a locus of weak signaling in children.
Consistent with this view, the right AI also shows weaker causal
influences on the dorsolateral frontoparietal areas involved in
problem solving and weaker signaling, a phenomenon associ-
ated with lower levels of overall behavioral performance in
children (Supekar & Menon, 2012; Figure 12). These observa-
tions suggest that the functional maturation of AI pathways is a
critical process by which human brain networks reconfigure and
mature during development to support more flexible cognitive
control processes in adulthood (Uddin et al., 2011).
Deficits in SN function and its interaction with other neu-
rocognitive networks also play a significant role in many
neurodevelopmental disorders (Menon, 2011). For example,
characterization of the SN has turned out to be particularly
promising for identifying atypical development in children
with autism (Di Martino et al., 2009; Uddin et al., 2013), a
disorder with early-life onset and variable developmental
trajectory (Stefanatos, 2008). The SN shows significant hyper-
connectivity in children with autism, and critically, connec-
tivity in these networks can be used to reliably distinguish
children with autism from typically developing children
(Uddin et al., 2013). Notably, among all networks examined,
connectivity patterns of the SN show the highest classification
accuracy between children with autism and typically
developing children. The SNs functional organization also
predicts restricted and repetitive behavior scores one of the
core symptoms of childhood autism (Di Martino et al., 2009;
Uddin et al., 2013). Identification of the SN as a particular
locus of aberrant connectivity in autism is consistent with the
hypothesis that inappropriate assignment of saliency to exter-
nal stimuli or internal mental events by this network plays
a prominent role in developmental disorders (Menon &
Uddin, 2010).
More generally, aberrant detection of saliency linked to
weak development of signaling from the AI to key nodes of
the SN and default-mode network may be a particular source
of vulnerability for psychopathology in the developing brain
(Fair et al., 2012; Menon, 2011; Uddin & Menon, 2009). The
application of a SN-based model holds great promise for
the principled investigation of psychopathology in both the
developing and adult brains, as elaborated in the next section.
The SN in Psychopathology
SN Deficits Are Prominent in Psychopathology
Network models are now being widely used to characterize
deficits in a wide range of psychiatric and neurological disor-
ders (Menon, 2011). These studies have provided evidence for
prominent SN dysfunction in many psychopathologies,
including frontotemporal dementia, mood and anxiety disor-
ders, schizophrenia, drug addiction, and pain (Figure 13). In
addition, isolated lesions to the insula have been associated
with dysfunction in autonomic function; gustatory, olfactory,
auditory, somatosensory, and multimodal perception; body

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606 INTRODUCTION TO SYSTEMS | Salience Network

Frontotemporal dementia
Salience network disruption

R FI z-scores
CDR sum of boxes

Schizophrenia
Gray matter signal
decrease in first
episode schizophrenia
Gray matter signal
decrease in first
episode and chronic
schizophrenia
Gray matter signal Reduced connectivity
decrease in chronic
schizophrenia
IPL

TPJ

SubC
AIns
MidT

Depression
MDD CTL MDD vs. CTL

Frequency

Intensity

Figure 12 SN dysfunction in major psychopathology. (A) Frontotemporal dementia: (a) SN connectivity disruption in patients with bvFTD. Multiple
nodes of the SN, including the FIC, lateral orbitofrontal cortex (lOFC), dorsal AI (dAI), midcingulate cortex (MCC), VStr, basolateral amygdala
(blAmy), thalamus, SuN/VTA, PAG, and dorsal pons and parabrachial nuclei (PBN), showed deficits in the patient group. (b) Of these regions, only the
right FIC responses were associated with functional severity, as measured by the Clinical Dementia Rating (CDR) scale, sum of boxes score.
Adapted from Zhou, J., Greicius, M. D., Gennatas, E. D., Growdon, M. E., Jang, J. Y., Rabinovici, G. D., et al. (2010). Divergent network connectivity
changes in behavioural variant frontotemporal dementia and Alzheimers disease. Brain: A Journal of Neurology, 133, 13521367. (B) Schizophrenia: (a)
Both functional and anatomical deficits are prominent in patients with schizophrenia. SN structural deficits in the insula and ACC are prominent in
both the early and late stages of schizophrenia, with progressive increase in gray matter deficits in chronic schizophrenia. Adapted from Ellison-Wright,
I., Glahn, D. C., Laird, A. R., Thelen, S. M., & Bullmore, E. (2008). The anatomy of first-episode and chronic schizophrenia: An anatomical likelihood
estimation meta-analysis. The American Journal of Psychiatry, 165, 10151023. (b) Significantly reduced functional connectivity in patients compared
with controls both within the SN (between AI and ACC) and with other networks (AI and vmPFC). AIns, anterior insula; IPL, inferior parietal lobule;
MidT, middle temporal; SubC, subcentral; TPJ, temporoparietal junction. Adapted from White, T. P., Joseph, V., Francis, S. T., & Liddle, P. F.
(2010). Aberrant salience network (bilateral insula and anterior cingulate cortex) connectivity during information processing in schizophrenia.
Schizophrenia Research, 123, 105115. (C) Depression: (a) SN and CEN activation (yellow-red) and DMN deactivation (blue-cyan) in patients with major
depressive disorder (MDD) and control (CTL) participants. (b) Chi-square statistic map showing increased frequency of inclusion of right FIC in the
SN and CEN in the MDD group. Adapted from Hamilton, J. P., Furman, D. J., Chang, C., Thomason, M. E., Dennis, E., & Gotlib, I. H. (2011). Default-mode
and task-positive network activity in major depressive disorder: Implications for adaptive and maladaptive rumination. Biological Psychiatry, 2, 2.
Brain Mapping: An Encyclopedic Reference, (2015), vol. 2, pp. 597-611
 Author's personal copy
INTRODUCTION TO SYSTEMS | Salience Network 607

rAI to rPPC

A Children B Adults C Adults > children B Child

rAI rAI rAI

A
ACC ACC ACC

Fiber density (105)

rPPC rPPC rPPC 10
rDLPFC rDLPFC rDLPFC 8
6 C Adult
4
rVLPFC rVLPFC rVLPFC 2
Children Adults
Directed influence
(relative to max) 100% 80% 60% 40% 20%
(a)

(b)

Reaction time Accuracy

Predictive causal Mean square Predictive causal Mean square

connections R2 error p connections R2 error p

Children rAIrDLPFC 0.50 0.75 <0.01 rAIrACC 0.43 0.83 <0.01

rAIrACC rAIrPPC

rAIrPPC rAIrVLPFC

Adults rAIrPPC 0.66 0.54 <0.01 rAIrACC 0.47 0.76 <0.01

rAIrVLPFC rAIrPPC

Relationship between cumulative directed causal influences between nodes of the salience and central executive networks and behavior assessed using a multivariate
GLMnet model. rAI = right anterior insula, ACC = anterior cingular cortex, rVLPFC = right ventrolateral prefrontal cortex, rDLPFC = right dorsolateral prefrontal cortex,
rPPC = right posterior parietal cortex. Analysis of GLMnet model fits revealed that causal network interactions better predicted reaction times and accuracy in adults
than in children.
Note: Connections ordered in decreasing order of importance.
(c)

Figure 13 Developmental changes in salience network organization and links to cognition. (A) Dynamic causal interactions network analysis using
state-space multivariate dynamical systems (MDS) model in (a) children and (b) adults. (c) Weaker causal interactions in children, compared with
adults. (B) Developmental changes in white matter tracts linking the AI and posterior parietal cortex. (a) Fiber density, the number of fibers per unit area,
between the rAI (yellow) and rPPC (red) is significantly lower in children, compared to adults (**p < 0.01). Tracts connecting the rAI to the rPPC
(cyan tracts) are shown in (b) children and (c) adults. (C) SN causal network interactions predict behavior differently in children and adults. Adapted
from Supekar, K., & Menon, V. (2012). Developmental maturation of dynamic causal control signals in higher-order cognition: A neurocognitive
network model. PLoS Computational Biology, 8, e1002374.

awareness; the emotion of disgust; mood and willed action;
and addiction (Ibanez, Gleichgerrcht, & Manes, 2010). I discuss
a few examples here from recent advances in network modeling
of the dementias, schizophrenia, and mood disorders.
Systematic investigation of the SN has provided better dif-
ferentiation of neurodegenerative disorders including fronto-
temporal dementia (Zhou et al., 2010). Of particular note is
behavioral variant frontotemporal dementia, which leaves
patients unable to model the emotional impact of their own
actions or inactions and involves progressive breakdown of the
SN arising from an initial core of frontoinsular degeneration
(Seeley, 2010). Crucially, this pattern of degeneration shows a
divergent pattern of changes from Alzheimers disease, which
has its primary origins in default-mode network dysfunction
(Zhou & Seeley, 2014).
In schizophrenia, both functional and structural studies
have pointed to dysfunctional organization of the SN. Bilateral
volume reduction in the AI and dACC nodes of the SN has
been detected in individuals with schizophrenia (White,
Joseph, Francis, & Liddle, 2010), and this reduction has been
linked to the severity of reality distortion (Palaniyappan,
Mallikarjun, Joseph, White, & Liddle, 2010). Aberrant intrinsic
functional connectivity of the SN and its interactions with
other networks has been found in patients with schizophrenia
(Manoliu et al., 2014) and younger adults at risk for psychosis
(Wotruba et al., 2013). Notably, conceptualization of psycho-
sis as aberrant signaling of salient events (Kapur, 2003) has led
researchers to propose that abnormalities in the attribution of
salience to external and internal stimuli are a core feature of
schizophrenia and may explain the genesis of psychotic symp-
toms such as delusions and hallucinations (Palaniyappan &
Liddle, 2012).
SN abnormalities are also prominent in mood and anxiety
disorders. Depressed subjects with high apathy show decreased
intrinsic connectivity of the SN, which suggests an important
role for the network in motivated behavior (Yuen et al., 2014).
The role of the SN in mood disorders is further highlighted by
findings that all the major nodes of the SN are affected in
patients with major depression, leading to the suggestion that
the occurrence of repetitive, preservative, negative thinking and
biases in attention to negative events may underlie aberrant SN
response and connectivity in the disorder (Hamilton, Chen, &
Gotlib, 2013). In anxiety disorders, hyperactivity of the AI
node of the SN has been consistently detected in patients
(Paulus & Stein, 2006; Stein, Simmons, Feinstein, & Paulus,
2007), and intrinsic functional connectivity analyses have

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608 INTRODUCTION TO SYSTEMS | Salience Network

demonstrated alterations within the SN in patients with gen-
eralized anxiety disorder (GAD) and social anxiety disorder
and posttraumatic stress disorder (Peterson, Thome, Frewen,
& Lanius, 2014). These findings are important because anxiety
disorders are a common comorbid feature of many psychiatric
disorders, including depression, phobia, and posttraumatic
stress disorder (Antony & Stein, 2009).
Taken together, these findings suggest that SN dysfunction
is a prominent feature of many psychiatric and neurological
disorders. In particular, the SN appears to be closely associated
with disorders in which attribution of saliency to biologically
and cognitively relevant stimuli are disrupted.
Saliency Mapping Deficits as an Integrative Model
for Psychopathology
The identification of SN dysfunction across multiple disorders
suggests basic network-level mechanisms by which aberrations
in this system can contribute to cognitive and affective dysfunc-
tion. Specifically, the characterization of the AI as a dynamic
causal hub for initiating network switching has provided novel
insights into mechanisms underlying deficits in cognitive
functioning in which (1) SN integrity and/or connectivity is
compromised as in frontotemporal dementia or (2) stimulus/
event salience is (a) weakly mapped as in autism or (b) errone-
ously mapped as in addiction, anxiety, or pain (Figure 14).
Signaling deficits can arise from aberrant filtering and mapping
of salient stimulus cues into the SN and weak signaling mech-
anisms from the SN to other networks such as the lateral fronto-
parietal central executive network. These signaling mechanisms
together with poor integrity of network nodes and their ana-
tomical connectivity (e.g., the posterior cingulate cortex and
medial temporal lobe nodes of the default-mode network in
Alzheimers disease or the ventromedial prefrontal cortex in
depression) can compromise interactions between these core
networks. Diminished outflow from the cingulate cortex results
in psychomotor poverty and impoverished goal-directed
action. Weak interactions along the anteriorposterior axis of
the insular cortex contribute to altered introspective awareness
and physiological monitoring of the internal milieu. The con-
sequence of abnormalities at any of these levels is deficient,
context-dependent engagement and disengagement of cogni-
tive systems important for attending to salient external stimuli
or internal mental events.

Improverished cognition
DLPFC (e.g., working memory,
sequential chaining)

Weak salience
mapping

Top-down

AI PI
PPC
Sensory
(e.g., novel, deviant)

Limbic
(e.g., reward, motivation) ACC VMPFC

Self-referential
(e.g., internal value,
autobiographical memory)

Psychomotor poverty
and impoverished
goal-directed action
Deficits in
PCC self-referential mental activity
(e.g., excessive rumination,
poor autobiographical
memory)

Figure 14 Salience network-based model of major psychopathology. Aberrant intrinsic organization and interconnectivity of the salience network (SN),
central executive network (CEN), and default-mode network (DMN) are characteristic of many psychiatric and neurological disorders. The model
proposes that weak salience detection and mapping of goal-relevant external stimuli and internal mental events from, and into, the SN play a major role
in psychopathology. Weak mapping from the insularcingulate SN gives rise to aberrant engagement of the frontoparietal CEN, compromising
cognition and goal-relevant adaptive behavior. Aberrant DMN organization and weak engagement or disengagement of the DMN by salient events are
associated with altered self-referential mental activity (e.g., excessive rumination in patients with depression). Weak salience mapping can arise
from at least three input factors: (i) aberrant stimulus mapping, such as weak or enhanced cue signaling and novelty detection; (ii) aberrant limbic
reward and motivational signals; and (iii) aberrant self-referential mental processes representing internal value and autobiographical memory. Key nodes
of the SN: AI and ACC; key nodes of the CEN: dlPFC and the PPC; key nodes of the DMN: vmPFC and PCC. Adapted from Menon, V. (2011). Large-scale
brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15, 483506.

Brain Mapping: An Encyclopedic Reference, (2015), vol. 2, pp. 597-611

 Author's personal copy
Conclusions
The SN is situated at the interface of the cognitive, homeostatic,
motivational, and affective systems of the human brain. It
plays a crucial role in identifying the most biologically and
cognitive relevant endogenous and external stimuli in order
to adaptively guide behavior (Beissner, Meissner, Bar, &
Napadow, 2013; Lovero, Simmons, Aron, & Paulus, 2009;
Menon & Uddin, 2010; Seeley et al., 2007; Sridharan et al.,
2008). With the AI as its dynamic hub, the SN contributes to a
variety of complex brain functions through the integration of
sensory, emotional, and cognitive information. The mecha-
nisms by which the SN contributes to cognitive and affective
function can be summarized as follows:
1. Detection of salient events by the AI via differential sensory
input and links with subcortical nodes involved in signal-
ing reward, motivation, and affective saliency
2. Functional coupling of the AI with the dACC to facilitate
rapid access to the motor system
3. Interaction of the AI with other insula subdivisions to
mediate physiological reactivity to, and interoceptive
awareness of, salient stimuli
4. Control signals to other large-scale networks that facilitate
access to working memory resources
5. Switching between the lateral frontoparietal central execu-
tive network and the medial frontoparietal default-mode
network to keep attention focused on task-relevant goals.
Together, these processes allow the SN to function collectively as
a key brain system for integrating cognition, action, and feelings.
Acknowledgments
It is a pleasure to thank Drs. Tanya Evans, Daniel Abrams, and
Aarthi Padmanabhan for their valuable feedback, Neha Vel-
lanki for proofreading, and Sandhya Prathap and Tricia Ngoon
for their assistance with the figures.
See also: INTRODUCTION TO ACQUISITION METHODS:
Functional MRI Dynamics; INTRODUCTION TO ANATOMY AND
PHYSIOLOGY: Insular Cortex; INTRODUCTION TO CLINICAL
BRAIN MAPPING: Frontotemporal Dementias; Functional Studies of
Parkinsons Disease; The Anatomy of Parkinsonian Disorders;
INTRODUCTION TO COGNITIVE NEUROSCIENCE: Attentional
Capacity and Limitations; Response Inhibition; Reward Processing;
Salience/Bottom-Up Attention; Task Switching Processes; Top-Down
Suppression; INTRODUCTION TO METHODS AND MODELING:
Resting-State Functional Connectivity; INTRODUCTION TO SOCIAL
COGNITIVE NEUROSCIENCE: Empathy; Neural Correlates of Social
Cognition Deficits in Autism Spectrum Disorders; INTRODUCTION TO
SYSTEMS: Autonomic Control; Emotion; Hubs and Pathways; Large-
Scale Functional Brain Organization; Neural Networks Underlying Novelty
Processing.
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